The problem of the combating virus infections has not yet been completely solved. One of the unsolved problems is the relatively rapid mutation of viruses which totally or partly prevents the effect of antiviral drugs or the body's own antibodies. One method to produce resistance against the most diverse types of multiviral infections is to use an "active substance cocktail" with which it is likely that one of the active substances will be efficacious. This principle has been put into practice by the SANDOZ company as the gamma-gobulin preparation, Sandoglobulin. This is a mixture of antibodies from the blood of more than 2000 Central European donors which exhibits a large portion of the spectrum of antibodies against diseases found in the Central European region. This product is therefore presumed to be effective against the most varied of infections because of its large number of different types of antibodies.
Previous attempts at combating virus infections have involved acting on different points in the virus replication process. For example, there are medicaments of the azidothymidine (AZT) type which inhibit reverse transcription by breaking chains. Unfortunately these medicaments lead to considerable side effects in patients.
International studies with dextran sulphate (compounds of saccharide and sulphur with approx. 10 kD) from plant hemicelluloses have shown that this group of substances represents no practical progress for the treatment of HIV patients.
Oral medication with dextran sulphate is problematic among other things because the dextran routes in the bloodstream and its concentration at the site of contract with the virus are not very effective. It also possesses very serious side effects (neuropenia, diarrhea). Clinically as well, no impressive effects could be established.
Attempts have already been made to use genetic engineering to produce isolated CD4 receptor proteins which would bind firmly on the gp 120 virus and therefore neutralize and inactivate it by means of saturation. In order to use this artificial CD4 as a therapeutic agent, however, it would be necessary to inject the artificial protein in high doses. The artificially high excess concentration of a cell sensor which is normally found outside of the membrane of healthy cells represents a multifaceted source of irritation for an organism whose immunological and other reactions cannot be ignored. Soluble CD4 could also bind at the MHC-II glycoproteins and impair their normal function. This could, for example, further increase the seriousness of the immunological deficiency in AIDS patients. In addition, soluble CD4 would have to be repeatedly administered parenterally with a high dosage (Spektrum der Wissenschafi--Dec. 88, p. 116).
One solution to this problem which has been suggested is to produce small sections of the CD4 protein fragments which would be structured in such a way that they would still be recognized by gp 120. If this was successful, the question would still remain of whether this protein fragment might not lead in vivo to immunological counter-regulation and elicit presently unknown disorders in the very lablie AIDS patient.
In 1990, M. LANGE (USA, also see Arztliche Praxis 15, p. 28 if., Werk-Verlag, D-8032 Gr afelfing) made it clear that with AIDS and ARC patients, the way to the point of no return is by no means a question of the virus production. Presumably HIV acts as an antigen and starts immunological pathomechanisms in motion which tend to escalate. Similarities with autoimmune diseases (e.g. lupus erythematosus)indicate that it cannot be sufficient only to administer anti-HIV chemotherapy. Rather it seems indispensable to include a provision for this development of autoimmunological independence (perpetuation) in the therapy and therefore to design and develop a new form of "anti-escalatory chemotherapy".
According to LANGE, extreme complementary activation occurs in the context of an HIV infection; the anaphylaxis factor C5 a induces the production of tumor necrosis factor and interleukin 1. HIV can cause this cascade to escalate. This has been proven by several groups of researchers. It follows from this finding that a promising anti-HIV chemotherapy must not be restricted solely to HIV inhibition. Rather it must also at least partially interrupt these kinds of autoimmunological by vicious circle mechanisms.
The individual escalatory interaction of the diverse noxae (HIV, causes of opportunistic infections, autoimmune cascades, etc.) must be better understood before a truly curative "chemotherapy" is possible. Only in this way can new treatment approaches be developed.
The success statistics of the current treatments (e.g. mean life expectancy after infection of 13-18 months, 5-year survival rate of 3.4% (San Francisco 1981-87, 4000 patients, published in the J. Amer. Med. Assoc. 263 (1990), 402), indicate that the present purely chemotherapeutically-oriented methods are not satisfactory.
W. J. Mach, the inventor, already demonstrated together with WITTICH and STUHLFAUTH in 1961 that small quantities (parenteral) of the natural pigments of the neo-penichromine type described by MACH act as "endogenous control substances" in human beings and, for example, increase the activity of the adrenal cortex.
This is presumably the first indication that redox pigments with quinoid units might be able to stimulate human "anti-escalatory" mechanisms without being itself a protein or hormone and without doing so by means of a nonspecific stimulation effect.
Therefore a future HIV chemotherapy must also (from the immunological perspective) contain anti-escalatory elements to inhibit development towards "the point of no return".
The aim of the invention is to find an active substance, if possible one which can also be administered parenterally, which can achieve a neutralization of the virus without cytotoxicological effects and without eliciting undesirable immunological reactions in the treated patient.
Another aim of the invention is to find an active substance which might also be active against changed/mutated virus forms.